For nanoparticle agglomerates, the catalytic activity may depend strongly on their structure. The influence of different parameters such as agglomerate structure, primary particle temperature history and surface preconditioning on the catalytic activity of nanoparticles was investigated. The fraction of agglomerate surface contributing to the reaction depends on the agglomerate structure and on the velocity of the reaction under investigation. For extremely fast reactions such as the oxidation of hydrogen on Pt nanoparticles, only the outermost surface (exposed surface) contributes substantially to the formation of water. For the system investigated here, the inner surface not substantially contributing to the reaction accounted for at least 70% of the total particle surface as determined from oxygen presaturation experiments of the agglomerate surface. A considerable activity loss of the platinum particles was observed on preheating the nanoparticle agglomerates. The preheating leads to an increase in the nanoparticle size by an order of magnitude due to sintering. It is unclear if this activity reduction is due to changes in the particle surface state or to a real size effect of the nanoparticles.